Marlon Brando was 66 in “The Freshman”.
The OP specifically says about men who are 65 or older.
If I eliminate movies in which Woody Allen doesn’t appear at all or only appears in a small role, I get the following by cutting down my previous list. I won’t try eliminating those that aren’t comedies. Most of his later films are both comedies and dramas:
Small Time Crooks (2000)
Picking Up the Pieces (2000)
The Curse of the Jade Scorpion (2001)
Hollywood Ending (2002)
Anything Else (2003)
Fading Gigolo (2013)
So Allen wasn’t playing “That Old Jewish Guy for decades, kvetching like he’s Jackie Mason’s grandfather”. He wasn’t that old in the films you’re thinking of. If you’re going to tell me that he was figuratively an Old Jewish Guy in those films, I would have to say that you don’t understand a certain stereotype that he plays. He played a Jewish man of whatever age he was at the time who liked to talk, mostly about his complaints. I’m not even sure that this stereotype is particularly Jewish.
Leo McKern played the title character of the TV legal [comedic rather than comic] series Rumpole of the Bailey into his 70s.
Would *Nebraska *fit as a comedy, especially as Bruce Dern won an Oscar for it at 76?
Three years after Harry and Tonto Art Carney did The Late Show with Lily Tomlin, which is hilarious
One of my favorite movies, although I’d argue that at heart it’s not a comedy. Newman deserved an Oscar.
My nomination is On Golden Pond, with knockout performances by Henry Fonda (76) and Katherine Hepburn (74). The rest of the cast wasn’t too shabby, either. 
Although the OP said 65+, I was going to say Spenser Tracy in Deck Set (1957), but he was born in 1900. Although he was 57 in the movie, he seemed much older to me.
OK - how about “Guess Who’s Coming to Dinner”, in 1967. He was 67 and died shortly after completing the film. IMDB lists it as a comedy-drama, so I guess that counts.
Now largely forgotten, George Arliss was born in 1868, meaning he was 65 or older in the last 12 movies he made, four of which were comedies: The King’s Vacation, The Working Man, The Last Gentleman, Mister Hobo. Having not seen any of them all the way through, I can’t say if they were “great” comedies or not, but I have seen Mr. Arliss in other movies and he had a formidable talent, particularly with sardonic humor.
I’m sure that Plan 9 From Outer Space wasn’t intended to be a comedy, but it comes across that way. Bela Lugosi was not intended to be the star, and footage of him was actually shot just before his death, several years before the film was ever made. Nonetheless, he was given film credit and is closely associated with the movie. Some of the scenes that he was supposedly in were filmed with a double who always had the cape across his face to hide the fact, which is funny in itself. Lugosi was 73 when his silent footage was done.
I don’t see it mentioned, and Walter Matthau was only 63, but…
Dustin Hoffman was born in 1937, which means he was past 65 for all the Fockers movies. Robert DeNiro is six years younger, but turned 65 in time for* Little Fockers*.
Another under-aged cheat, but 62-year old Richard Farnsworth in The Grey Fox.
In what sense is The Grey Fox a comedy?
We’ve mentioned several Walter Matthau and George Burns movies, but somehow missed one they were in together: The Sunshine Boys
George Burns was in his 80s and the film started his “second act”, introducing him to a new generation. He kept working until shortly before his death at 100. Matthau was considerably younger at the time it was made (1975), but certainly looked the part.
The scene in which Burns and Matthau meet to rehearse their old sketch is slow-motion comedy of the best kind. Later, we see them turn it on while rehearsing at the TV studio and it’s like watching a Vaudeville act in color. One of my favorite films.
Another too-young Walter Matthau in Hopscotch.
Nominee, not winner.
2013 was one of those rare years where they all deserved it.
Cary Grant in Charade, opposite Audrey Hepburn. He was a lot older than 37.
If we’re going by age difference and not by the actual age of the male lead, that’s most comedies where the characters are supposed to be adults and 90%+ of those in which they’re supposed to be teenagers…
It’s typical in movies of many sorts for the male lead to be older, often much older, than the female lead, as in the examples cited here: